ORYZON presents iadademstat ALICE 30-month data at EHA-2021, confirming positive and robust efficacy in combination with azacitidine in AML
- Robust signals of clinical efficacy, with ORR of 83%, of which 67% areCR/CRi
- Five patients with responses longer than 1 year
- Longest remission 858 days, still ongoing
- Rapid onset of responses (TTR 29 days)
- Iadademstat and azacitidine combination shows a good safety profile
MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, June 11th, 2021 - Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, presented today new positive efficacy data from its ongoing Phase IIa ALICE trial, which is investigating iadademstat in combination with azacitidine in elderly or unfit patients with acute myeloid leukemia (AML). The data were presented at the virtual EHA-2021 Conference, in an e-poster entitled “ALICE MAINTAINS HIGH CLINICAL RESPONSE RATES SUPPORTING THE EFFICACY OF IADADEMSTAT COMBINATION WITH AZACITIDINE IN AML MANAGEMENT”.
Twenty-seven patients (median age 77 years) had been enrolled in the trial up to May 24th and are reported in these data, one of whom did not fulfill the inclusion criteria. Eighteen patients were evaluable for efficacy as per protocol and two more were still in Cycle-1. The evidence of clinical efficacy continues to be robust and consistent with previously reported data, with an objective response rate (ORR) of 83% (15 out of 18 evaluable patients); of these, 67% were complete remissions (10 CR/CRi), and 33% partial remissions (5 PR). Of note, one patient with M5b (monocytic) AML, a traditional hard-to-treat leukemia subgroup and who also had an adverse prognosis, achieved CRi in 29 days. Mean Time to Response (TTR) was only 29 days.
With historical response rates of 28% in this population when treated with azacitidine alone (19% CR/CRi and 9% PRs), these results support a strong synergy between iadademstat and azacitidine when used in combination.
The duration of the observed responses is also encouraging, with 60% of the CR/CRi lasting more than 6 months. The current longest remission at the data cut-off date for the EHA-2021 communication was 858 days in a patient that continues transfusion independent and MRD-negative. Four other patients have achieved responses longer than 1 year (3 still ongoing). Those patients with longer treatment periods have also improved or overcome their dependency on blood transfusions, with 50% of the CR/CRi patients already transfusion independent.
Dr. Carlos Buesa, Oryzon’s CEO, said: "We are pleased with these very positive data from the ALICE trial after 30 months of study and with a growing number of patients enrolled, confirming a robust high percentage of responses. We also see these responses maturing in longer times of remission, which extends survival. Considering the different mechanisms of action of proapoptotic BCL2 inhibitors and the pro-differentiating agent iadademstat, we believe that combination approaches with iadademstat will increase therapeutic options for AML patients in first line, as well as for refractory or intolerant patients who have received BCL2 inhibitors as first line.”
The combination of iadademstat with azacitidine continues to show a good safety profile with only two serious adverse events reported as probably related to treatment. The most frequent events continue to be a decrease in the platelet and neutrophil count. Besides the expected hematological impact, in line with the pharmacologic mode of action and previously presented at ASH 2020 and EHA-2020, the combination continues to appear safe and well tolerated by elderly AML patients.
The purpose of the ALICE trial is to inform the broader use of iadademstat in leukemia. ALICE is designed as a single-arm, open-label study of iadademstat in combination with the standard of care treatment azacitidine in newly diagnosed elderly or unfit AML patients and is being carried out in eight Spanish hospitals. The study will recruit up to a maximum of 36 patients.
A copy of the EHA-2021 poster is available here
Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company considered as the European champion in Epigenetics. Oryzon has one of the strongest portfolios in the field. Oryzon’s LSD1 program has rendered two compounds, vafidemstat and iadademstat, in Phase II clinical trials. In addition, Oryzon has ongoing programs for developing inhibitors against other epigenetic targets. Oryzon has a strong technological platform for biomarker identification and performs biomarker and target validation for a variety of malignant and neurological diseases. Oryzon has offices in Spain and the United States. Oryzon is one of the most liquid biotech stocks in Europe with +90 M shares negotiated in 2020 (ORY:SM / ORY.MC / ORYZF US OTC mkt). For more information, visit www.oryzon.com
Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (See Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A first Phase I/IIa clinical trial with iadademstat in refractory and relapsed acute leukemia patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors, medulloblastoma and others. Iadademstat has been tested in four clinical trials (two in monotherapy in SCLC and AML, and two in combination, in SCLC and AML) in more than 100 patients. In the combination studies, ALICE (ongoing), a Phase IIa trial in combination with azacitidine in elderly or unfit AML patients, and CLEPSIDRA (finalized), a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients, preliminary efficacy results have been reported.
This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements.